Project Summary Racial disparities exist in cognitive aging, and it has been established that long-term HIV disease accelerates cognitive aging processes. African Americans (AAs) are a particularly vulnerable group, and our preliminary data indicate that HIV+ AAs demonstrate worse cognitive and brain imaging outcomes than HIV+ EAs even after controlling for confounding factors. We do not know if these disparities persist over time, and the reasons for racial disparities in cognitive outcomes remains unclear. It is well-known that lifetime exposure to stress, which is associated with HIV-infection and AA race, influences cognitive outcomes. Thus, we hypothesize that lifetime stress is a mechanism that places HIV+ AAs at risk for poor cognitive outcomes. Peripheral inflammation has been linked to cognitive impairment in several studies, and is increased in association with HIV, AA race, and lifetime stress. Prospective studies are needed to determine if HIV, lifetime stress exposure and AA race results in premature cognitive aging via increased inflammation. The present study will address this gap in knowledge by examining rates of change in cognitive function and cortical and subcortical brain structures in a cohort of 250 older adults (50+) with and without HIV infection stratified by ethnicity (AA vs. EA). We will also address the gaps in the current stress and disparities literature by using a comprehensive measure of stress and adversity over the lifespan (i.e., Stress and Adversity Inventory [STRAIN]). The STRAIN will allow us to capture stressors that have occurred over an individual's lifetime as well as new stressors during the course of the study. We will examine how recent stress exposure is associated with changes in inflammation and cognitive/brain outcomes. This study is highly significant, as no study to date has examined racial disparities in risk for cognitive declines in HIV-seropositive individuals. We will use state-of-the art methods for measuring brain changes by following up on a cohort of older (aged 50+) HIV+ and HIV- individuals from a previous NIH supported study. Structural neuroimaging will be used to examine longitudinal changes in morphometry and regional connectivity. The primary aim of this study is to evaluate the prospective change in brain/cognitive function in HIV+ and HIV- adults stratified by AA and EA race. Our secondary aim is to determine how lifetime stress differs as a function of HIV status and race. Our third aim will examine how life stress is associated with prospective changes in cognition/brain structure. Finally, we will examine associations between recent life stress and changes in inflammation, and how these changes in inflammation influence cognitive/brain outcomes. This project brings together the skills of several research groups at UCLA, and builds upon existing collaborations and resources. To our knowledge, this is the first prospective study to evaluate cognitive aging in a large cohort of HIV+ and HIV- AA and EA older adults. At the end of this study we expect to discern the relative contributions of AA and HIV-specific processes as these unfold via inflammatory processes that increase vulnerability to premature aging.